ID TSHR_HUMAN Reviewed; 764 AA. AC P16473; A0PJU7; F5GYU5; G3V2A9; Q16503; Q8TB90; Q96GT6; Q9P1V4; Q9ULA3; AC Q9UPH3; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 29-MAR-2005, sequence version 2. DT 27-MAR-2024, entry version 254. DE RecName: Full=Thyrotropin receptor; DE AltName: Full=Thyroid-stimulating hormone receptor; DE Short=TSH-R; DE Flags: Precursor; GN Name=TSHR; Synonyms=LGR3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RX PubMed=2558651; DOI=10.1016/0006-291x(89)92727-7; RA Nagayama Y., Kaufman K.D., Seto P., Rapoport B.; RT "Molecular cloning, sequence and functional expression of the cDNA for the RT human thyrotropin receptor."; RL Biochem. Biophys. Res. Commun. 165:1184-1190(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND TISSUE SPECIFICITY. RC TISSUE=Thyroid; RX PubMed=2610690; DOI=10.1016/0006-291x(89)92736-8; RA Libert F., Lefort A., Gerard C., Parmentier M., Perret J., Ludgate M., RA Dumont J.E., Vassart G.; RT "Cloning, sequencing and expression of the human thyrotropin (TSH) RT receptor: evidence for binding of autoantibodies."; RL Biochem. Biophys. Res. Commun. 165:1250-1255(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND VARIANT GLU-727. RX PubMed=2302212; DOI=10.1016/0006-291x(90)91958-u; RA Misrahi M., Loosfelt H., Atger M., Sar S., Guiochon-Mantel A., Milgrom E.; RT "Cloning, sequencing and expression of human TSH receptor."; RL Biochem. Biophys. Res. Commun. 166:394-403(1990). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RC TISSUE=Thyroid; RX PubMed=2293030; DOI=10.1210/mend-4-8-1264; RA Frazier A.L., Robbins L.S., Stork P.J., Sprengel R., Segaloff D.L., RA Cone R.D.; RT "Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation RT by tissue specific splicing."; RL Mol. Endocrinol. 4:1264-1276(1990). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RX PubMed=1530609; DOI=10.1016/0006-291x(92)91315-h; RA Graves P.N., Tomer Y., Davies T.F.; RT "Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor RT mRNA lacking the transmembrane domain."; RL Biochem. Biophys. Res. Commun. 187:1135-1143(1992). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RC TISSUE=Thyroid; RX PubMed=1445355; DOI=10.1016/0006-291x(92)91360-3; RA Takeshita A., Nagayama Y., Fujiyama K., Yokoyama N., Namba H., RA Yamashita S., Izumi M., Nagataki S.; RT "Molecular cloning and sequencing of an alternatively spliced form of the RT human thyrotropin receptor transcript."; RL Biochem. Biophys. Res. Commun. 188:1214-1219(1992). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC TISSUE=Thyroid; RA Kopatz S.A., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-727. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SHORT AND 3). RC TISSUE=Ovarian adenocarcinoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP PROTEIN SEQUENCE OF 66-80; 113-123; 184-210 AND 294-310, AND GLYCOSYLATION RP AT ASN-77; ASN-113; ASN-198 AND ASN-302. RX PubMed=11502179; DOI=10.1021/bi0107389; RA Cornelis S., Uttenweiler-Joseph S., Panneels V., Vassart G., RA Costagliola S.; RT "Purification and characterization of a soluble bioactive amino-terminal RT extracellular domain of the human thyrotropin receptor."; RL Biochemistry 40:9860-9869(2001). RN [11] RP FUNCTION, GLYCOSYLATION, SUBCELLULAR LOCATION, SULFATION AT TYR-385, TISSUE RP SPECIFICITY, AND MUTAGENESIS OF CYS-283; TYR-385 AND TYR-387. RX PubMed=11847099; DOI=10.1093/emboj/21.4.504; RA Costagliola S., Panneels V., Bonomi M., Koch J., Many M.C., Smits G., RA Vassart G.; RT "Tyrosine sulfation is required for agonist recognition by glycoprotein RT hormone receptors."; RL EMBO J. 21:504-513(2002). RN [12] RP FUNCTION, AND INTERACTION WITH HETERODIMER GPHA2-GPHB5. RX PubMed=12045258; DOI=10.1172/jci14340; RA Nakabayashi K., Matsumi H., Bhalla A., Bae J., Mosselman S., Hsu S.Y., RA Hsueh A.J.W.; RT "Thyrostimulin, a heterodimer of two new human glycoprotein hormone RT subunits, activates the thyroid-stimulating hormone receptor."; RL J. Clin. Invest. 109:1445-1452(2002). RN [13] RP INTERACTION WITH SCRIB. RX PubMed=15775968; DOI=10.1038/sj.emboj.7600616; RA Lahuna O., Quellari M., Achard C., Nola S., Meduri G., Navarro C., RA Vitale N., Borg J.-P., Misrahi M.; RT "Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 RT pathway."; RL EMBO J. 24:1364-1374(2005). RN [14] RP 3D-STRUCTURE MODELING OF 54-236. RX PubMed=8747461; DOI=10.1016/s0969-2126(01)00272-6; RA Jiang X., Dreano M., Buckler D.R., Cheng S., Ythier A., Wu H., RA Hendrickson W.A., el Tayar N.; RT "Structural predictions for the ligand-binding region of glycoprotein RT hormone receptors and the nature of hormone-receptor interactions."; RL Structure 3:1341-1353(1995). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 22-260 IN COMPLEX WITH ANTIBODY, RP GLYCOSYLATION AT ASN-77; ASN-99; ASN-113; ASN-177 AND ASN-198, AND RP N-TERMINAL DISULFIDE BOND. RX PubMed=17542669; DOI=10.1089/thy.2007.0034; RA Sanders J., Chirgadze D.Y., Sanders P., Baker S., Sullivan A., RA Bhardwaja A., Bolton J., Reeve M., Nakatake N., Evans M., Richards T., RA Powell M., Miguel R.N., Blundell T.L., Furmaniak J., Smith B.R.; RT "Crystal structure of the TSH receptor in complex with a thyroid- RT stimulating autoantibody."; RL Thyroid 17:395-410(2007). RN [16] RP ANALYSIS OF INVOLVEMENT OF VARIANT GLU-727 IN GRAVES DISEASE. RX PubMed=11887032; RA Chistiakov D.A., Savost'anov K.V., Turakulov R.I., Petunina N., RA Balabolkin M.I., Nosikov V.V.; RT "Further studies of genetic susceptibility to Graves' disease in a Russian RT population."; RL Med. Sci. Monit. 8:CR180-CR184(2002). RN [17] RP ANALYSIS OF INVOLVEMENT OF VARIANT GLU-727 IN GRAVES DISEASE. RX PubMed=12593721; DOI=10.1089/105072502321085171; RA Ban Y., Greenberg D.A., Concepcion E.S., Tomer Y.; RT "A germline single nucleotide polymorphism at the intracellular domain of RT the human thyrotropin receptor does not have a major effect on the RT development of Graves' disease."; RL Thyroid 12:1079-1083(2002). RN [18] RP ANALYSIS OF INVOLVEMENT OF VARIANTS HIS-36; THR-52 AND GLU-727 IN GRAVES RP DISEASE. RX PubMed=12930595; DOI=10.1089/105072503322238773; RA Ho S.-C., Goh S.-S., Khoo D.H.; RT "Association of Graves' disease with intragenic polymorphism of the RT thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic RT origins."; RL Thyroid 13:523-528(2003). RN [19] RP REVIEW ON VARIANTS. RX PubMed=10870027; DOI=10.1530/eje.0.1430025; RA Farid N.R., Kascur V., Balazs C.; RT "The human thyrotropin receptor is highly mutable: a review of gain-of- RT function mutations."; RL Eur. J. Endocrinol. 143:25-30(2000). RN [20] RP VARIANT HIS-36. RX PubMed=1955520; DOI=10.1210/jcem-73-6-1374; RA Heldin N.-E., Gustavsson B., Westermark K., Westermark B.; RT "A somatic point mutation in a putative ligand binding domain of the TSH RT receptor in a patient with autoimmune hyperthyroidism."; RL J. Clin. Endocrinol. Metab. 73:1374-1376(1991). RN [21] RP VARIANTS HYPERTHYROIDISM GLY-619 AND ILE-623. RX PubMed=8413627; DOI=10.1038/365649a0; RA Parma J., Duprez L., van Sande J., Cochaux P., Gervy C., Mockel J., RA Dumont J.E., Vassart G.; RT "Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning RT thyroid adenomas."; RL Nature 365:649-651(1993). RN [22] RP VARIANT THR-52. RX PubMed=7508946; DOI=10.1210/jcem.78.2.7508946; RA Bahn R.S., Dutton C.M., Heufelder A.E., Sarkar G.; RT "A genomic point mutation in the extracellular domain of the thyrotropin RT receptor in patients with Graves' ophthalmopathy."; RL J. Clin. Endocrinol. Metab. 78:256-260(1994). RN [23] RP VARIANTS HYPERTHYROIDISM CYS-631; ILE-632; GLU-633 AND TYR-633. RX PubMed=8045989; DOI=10.1210/jcem.79.2.8045989; RA Porcellini A., Ciullo I., Laviola L., Amabile G., Fenzi G., RA Avvedimento V.E.; RT "Novel mutations of thyrotropin receptor gene in thyroid hyperfunctioning RT adenomas. Rapid identification by fine needle aspiration biopsy."; RL J. Clin. Endocrinol. Metab. 79:657-661(1994). RN [24] RP VARIANTS HYPERTHYROIDISM VAL-623 AND ILE-632. RX PubMed=7989485; DOI=10.1210/jcem.79.6.7989485; RA Paschke R., Tonacchera M., van Sande J., Parma J., Vassart G.; RT "Identification and functional characterization of two new somatic RT mutations causing constitutive activation of the thyrotropin receptor in RT hyperfunctioning autonomous adenomas of the thyroid."; RL J. Clin. Endocrinol. Metab. 79:1785-1789(1994). RN [25] RP VARIANTS HTNA ALA-509 AND TYR-672. RX PubMed=7920658; DOI=10.1038/ng0794-396; RA Duprez L., Parma J., van Sande J., Allgeier A., Leclere J., Schvartz C., RA Delisle M.-J., Decoulx M., Orgiazzi J., Dumont J.E., Vassart G.; RT "Germline mutations in the thyrotropin receptor gene cause non-autoimmune RT autosomal dominant hyperthyroidism."; RL Nat. Genet. 7:396-401(1994). RN [26] RP CHARACTERIZATION OF VARIANT HIS-36. RX PubMed=7556878; DOI=10.1016/0303-7207(95)03562-l; RA Gustavsson B., Eklof C., Westermark K., Westermark B., Heldin N.-E.; RT "Functional analysis of a variant of the thyrotropin receptor gene in a RT family with Graves' disease."; RL Mol. Cell. Endocrinol. 111:167-173(1995). RN [27] RP VARIANT HTNA LEU-631. RX PubMed=7800007; DOI=10.1056/nejm199501193320304; RA Kopp P., van Sande J., Parma J., Duprez L., Gerber H., Joss E., RA Jameson J.L., Dumont J.E., Vassart G.; RT "Congenital hyperthyroidism caused by a mutation in the thyrotropin- RT receptor gene."; RL N. Engl. J. Med. 332:150-154(1995). RN [28] RP VARIANTS CHNG1 ALA-162 AND ASN-167, AND VARIANT THR-52. RX PubMed=7528344; DOI=10.1056/nejm199501193320305; RA Sunthornthepvarakul T., Gottschalk M.E., Hayashi Y., Refetoff S.; RT "Resistance to thyrotropin caused by mutations in the thyrotropin-receptor RT gene."; RL N. Engl. J. Med. 332:155-160(1995). RN [29] RP VARIANTS PAPILLARY CANCER ILE-197; GLU-219; ASP-715 AND MET-723, AND RP VARIANT GLU-727. RX PubMed=7647578; DOI=10.1089/thy.1995.5.97; RA Ohno M., Endo T., Ohta K., Gunji K., Onaya T.; RT "Point mutations in the thyrotropin receptor in human thyroid tumors."; RL Thyroid 5:97-100(1995). RN [30] RP VARIANT THR-52. RX PubMed=7488864; DOI=10.1089/thy.1995.5.255; RA Cuddihy R.M., Bryant W.P., Bahn R.S.; RT "Normal function in vivo of a homozygotic polymorphism in the human RT thyrotropin receptor."; RL Thyroid 5:255-257(1995). RN [31] RP VARIANTS HTNA ARG-505; TYR-650 AND SER-670. RX PubMed=8636266; DOI=10.1210/jcem.81.2.8636266; RA Tonacchera M., van Sande J., Cetani F., Swillens S., Schvartz C., RA Winiszewski P., Portmann L., Dumont J.E., Vassart G., Parma J.; RT "Functional characteristics of three new germline mutations of the RT thyrotropin receptor gene causing autosomal dominant toxic thyroid RT hyperplasia."; RL J. Clin. Endocrinol. Metab. 81:547-554(1996). RN [32] RP VARIANT HTNA THR-453. RX PubMed=8964822; DOI=10.1210/jcem.81.6.8964822; RA de Roux N., Polak M., Couet J., Leger J., Czernichow P., Milgrom E., RA Misrahi M.; RT "A neomutation of the thyroid-stimulating hormone receptor in a severe RT neonatal hyperthyroidism."; RL J. Clin. Endocrinol. Metab. 81:2023-2026(1996). RN [33] RP VARIANTS CHNG1 SER-41; ALA-162; TRP-390; ASN-410 AND LEU-525. RX PubMed=8954020; DOI=10.1210/jcem.81.12.8954020; RA de Roux N., Misrahi M., Brauner R., Houang M., Carel J.-C., Granier M., RA Le Bouc Y., Ghinea N., Boumedienne A., Toublanc J.E., Milgrom E.; RT "Four families with loss of function mutations of the thyrotropin RT receptor."; RL J. Clin. Endocrinol. Metab. 81:4229-4235(1996). RN [34] RP VARIANT INSULAR CARCINOMA HIS-633. RX PubMed=9062474; DOI=10.1210/jcem.82.3.3838; RA Russo D., Tumino S., Arturi F., Vigneri P., Grasso G., Pontecorvi A., RA Filetti S., Belfiore A.; RT "Detection of an activating mutation of the thyrotropin receptor in a case RT of an autonomously hyperfunctioning thyroid insular carcinoma."; RL J. Clin. Endocrinol. Metab. 82:735-738(1997). RN [35] RP VARIANT CHNG1 GLN-109. RX PubMed=9100579; DOI=10.1210/jcem.82.4.3863; RA Clifton-Bligh R.J., Gregory J.W., Ludgate M., John R., Persani L., RA Asteria C., Beck-Peccoz P., Chatterjee V.K.K.; RT "Two novel mutations in the thyrotropin (TSH) receptor gene in a child with RT resistance to TSH."; RL J. Clin. Endocrinol. Metab. 82:1094-1100(1997). RN [36] RP VARIANTS HYPERTHYROIDISM ASN-281; THR-281; THR-453; PHE-486; MET-486; RP THR-568; GLY-619; ILE-623; PHE-629; LEU-630; LEU-631; ILE-632; ALA-633; RP GLU-633; HIS-633; TYR-633 AND 658-ASN--ILE-661 DEL. RX PubMed=9253356; DOI=10.1210/jcem.82.8.4144; RA Parma J., Duprez L., van Sande J., Hermans J., Rocmans P., van Vliet G., RA Costagliola S., Rodien P., Dumont J.E., Vassart G.; RT "Diversity and prevalence of somatic mutations in the thyrotropin receptor RT and Gs alpha genes as a cause of toxic thyroid adenomas."; RL J. Clin. Endocrinol. Metab. 82:2695-2701(1997). RN [37] RP VARIANT CHNG1 TRP-390. RX PubMed=9329388; DOI=10.1210/jcem.82.10.4286; RA Biebermann H., Schoeneberg T., Krude H., Schultz G., Gudermann T., RA Grueters A.; RT "Mutations of the human thyrotropin receptor gene causing thyroid RT hypoplasia and persistent congenital hypothyroidism."; RL J. Clin. Endocrinol. Metab. 82:3471-3480(1997). RN [38] RP VARIANT HTNA ASN-505. RX PubMed=9360555; DOI=10.1210/jcem.82.11.4378; RA Holzapfel H.P., Wonerow P., von Petrykowski W., Henschen M., RA Scherbaum W.A., Paschke R.; RT "Sporadic congenital hyperthyroidism due to a spontaneous germline mutation RT in the thyrotropin receptor gene."; RL J. Clin. Endocrinol. Metab. 82:3879-3884(1997). RN [39] RP VARIANT HTNA PHE-629. RX PubMed=9398746; DOI=10.1210/jcem.82.12.4405; RA Fuhrer D., Wonerow P., Willgerodt H., Paschke R.; RT "Identification of a new thyrotropin receptor germline mutation (Leu629Phe) RT in a family with neonatal onset of autosomal dominant nonautoimmune RT hyperthyroidism."; RL J. Clin. Endocrinol. Metab. 82:4234-4238(1997). RN [40] RP VARIANT CHNG1 THR-553. RX PubMed=9185526; DOI=10.1172/jci119497; RA Abramowicz M.J., Duprez L., Parma J., Vassart G., Heinrichs C.; RT "Familial congenital hypothyroidism due to inactivating mutation of the RT thyrotropin receptor causing profound hypoplasia of the thyroid gland."; RL J. Clin. Invest. 99:3018-3024(1997). RN [41] RP VARIANT HYPERTHYROIDISM ILE-281. RX PubMed=9294132; DOI=10.1172/jci119687; RA Kopp P., Muirhead S., Jourdain N., Gu W.X., Jameson J.L., Rodd C.; RT "Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a RT novel somatic mutation (serine281-->isoleucine) in the extracellular domain RT of the thyrotropin receptor."; RL J. Clin. Invest. 100:1634-1639(1997). RN [42] RP VARIANT HTNA ILE-632. RX PubMed=9349581; DOI=10.1089/thy.1997.7.765; RA Kopp P., Jameson J.L., Roe T.F.; RT "Congenital nonautoimmune hyperthyroidism in a nonidentical twin caused by RT a sporadic germline mutation in the thyrotropin receptor gene."; RL Thyroid 7:765-770(1997). RN [43] RP VARIANT HTNA ASN-281, AND VARIANT HIS-528. RX PubMed=9589634; DOI=10.1210/jcem.83.5.4776; RA Grueters A., Schoeneberg T., Biebermann H., Krude H., Krohn H.P., RA Dralle H., Gudermann T.; RT "Severe congenital hyperthyroidism caused by a germ-line neo mutation in RT the extracellular portion of the thyrotropin receptor."; RL J. Clin. Endocrinol. Metab. 83:1431-1436(1998). RN [44] RP VARIANT HTFG ARG-183. RX PubMed=9854118; DOI=10.1056/nejm199812173392505; RA Rodien P., Bremont C., Raffin Sanson M.-L., Parma J., van Sande J., RA Costagliola S., Luton J.-P., Vassart G., Duprez L.; RT "Familial gestational hyperthyroidism caused by a mutant thyrotropin RT receptor hypersensitive to human chorionic gonadotropin."; RL N. Engl. J. Med. 339:1823-1826(1998). RN [45] RP VARIANT HTNA SER-639. RX PubMed=10199795; DOI=10.1210/jcem.84.4.5620; RA Khoo D.H.C., Parma J., Rajasoorya C., Ho S.C., Vassart G.; RT "A germline mutation of the thyrotropin receptor gene associated with RT thyrotoxicosis and mitral valve prolapse in a Chinese family."; RL J. Clin. Endocrinol. Metab. 84:1459-1462(1999). RN [46] RP VARIANTS MET-606; GLY-703; GLU-720 AND GLU-727. RX PubMed=10487707; DOI=10.1210/jcem.84.9.5966; RA Gabriel E.M., Bergert E.R., Grant C.S., van Heerden J.A., Thompson G.B., RA Morris J.C.; RT "Germline polymorphism of codon 727 of human thyroid-stimulating hormone RT receptor is associated with toxic multinodular goiter."; RL J. Clin. Endocrinol. Metab. 84:3328-3335(1999). RN [47] RP VARIANT THYROID CARCINOMA VAL-677. RX PubMed=10037070; DOI=10.1089/thy.1999.9.13; RA Russo D., Wong M.G., Costante G., Chiefari E., Treseler P.A., Arturi F., RA Filetti S., Clark O.H.; RT "A Val 677 activating mutation of the thyrotropin receptor in a Hurthle RT cell thyroid carcinoma associated with thyrotoxicosis."; RL Thyroid 9:13-17(1999). RN [48] RP VARIANT HYPERTHYROIDISM LEU-597. RX PubMed=10560955; DOI=10.1089/thy.1999.9.1005; RA Esapa C.T., Duprez L., Ludgate M., Mustafa M.S., Kendall-Taylor P., RA Vassart G., Harris P.E.; RT "A novel thyrotropin receptor mutation in an infant with severe RT thyrotoxicosis."; RL Thyroid 9:1005-1010(1999). RN [49] RP VARIANT HYPERTHYROIDISM ARG-512, AND CHARACTERIZATION OF VARIANT RP HYPERTHYROIDISM ARG-512. RX PubMed=11022192; DOI=10.1530/eje.0.1430471; RA Kosugi S., Hai N., Okamoto H., Sugawa H., Mori T.; RT "A novel activating mutation in the thyrotropin receptor gene in an RT autonomously functioning thyroid nodule developed by a Japanese patient."; RL Eur. J. Endocrinol. 143:471-477(2000). RN [50] RP VARIANT THR-52. RX PubMed=10651846; DOI=10.1046/j.1365-2370.2000.00187.x; RA Kaczur V., Takacs M., Szalai C., Falus A., Nagy Z., Berencsi G., Balazs C.; RT "Analysis of the genetic variability of the 1st (CCC/ACC, P52T) and the RT 10th exons (bp 1012-1704) of the TSH receptor gene in Graves' disease."; RL Eur. J. Immunogenet. 27:17-23(2000). RN [51] RP VARIANT CHNG1 ILE-477. RX PubMed=10720030; DOI=10.1210/jcem.85.3.6460; RA Tonacchera M., Agretti P., Pinchera A., Rosellini V., Perri A., RA Collecchi P., Vitti P., Chiovato L.; RT "Congenital hypothyroidism with impaired thyroid response to thyrotropin RT (TSH) and absent circulating thyroglobulin: evidence for a new inactivating RT mutation of the TSH receptor gene."; RL J. Clin. Endocrinol. Metab. 85:1001-1008(2000). RN [52] RP VARIANTS HTNA ASN-281; MET-486; PHE-486; PHE-629; ALA-632; ILE-632; GLU-633 RP AND VAL-647. RX PubMed=10852462; DOI=10.1210/jcem.85.6.6634; RA Tonacchera M., Agretti P., Chiovato L., Rosellini V., Ceccarini G., RA Perri A., Viacava P., Naccarato A.G., Miccoli P., Pinchera A., Vitti P.; RT "Activating thyrotropin receptor mutations are present in nonadenomatous RT hyperfunctioning nodules of toxic or autonomous multinodular goiter."; RL J. Clin. Endocrinol. Metab. 85:2270-2274(2000). RN [53] RP VARIANT GLU-727. RX PubMed=10946859; DOI=10.1210/jcem.85.8.6704; RA Muehlberg T., Herrmann K., Joba W., Kirchberger M., Heberling H.-J., RA Heufelder A.E.; RT "Lack of association of nonautoimmune hyperfunctioning thyroid disorders RT and a germline polymorphism of codon 727 of the human thyrotropin receptor RT in a European Caucasian population."; RL J. Clin. Endocrinol. Metab. 85:2640-2643(2000). RN [54] RP VARIANT CHNG1 CYS-310. RX PubMed=11095460; DOI=10.1210/jcem.85.11.6985; RA Russo D., Betterle C., Arturi F., Chiefari E., Girelli M.E., Filetti S.; RT "A novel mutation in the thyrotropin (TSH) receptor gene causing loss of RT TSH binding but constitutive receptor activation in a family with RT resistance to TSH."; RL J. Clin. Endocrinol. Metab. 85:4238-4242(2000). RN [55] RP VARIANTS HTNA ASN-281; SER-431 AND ILE-632. RX PubMed=11127522; DOI=10.1007/s004230000145; RA Biebermann H., Schoeneberg T., Krude H., Gudermann T., Grueters A.; RT "Constitutively activating TSH-receptor mutations as a molecular cause of RT non-autoimmune hyperthyroidism in childhood."; RL Langenbecks Arch. Surg. 385:390-392(2000). RN [56] RP VARIANT HTNA THR-568. RX PubMed=11081252; DOI=10.1089/thy.2000.10.859; RA Tonacchera M., Agretti P., Rosellini V., Ceccarini G., Perri A., RA Zampolli M., Longhi R., Larizza D., Pinchera A., Vitti P., Chiovato L.; RT "Sporadic nonautoimmune congenital hyperthyroidism due to a strong RT activating mutation of the thyrotropin receptor gene."; RL Thyroid 10:859-863(2000). RN [57] RP VARIANT FOLLICULAR CARCINOMA PHE-486. RX PubMed=11128715; DOI=10.1089/thy.2000.10.1009; RA Camacho P., Gordon D., Chiefari E., Yong S., DeJong S., Pitale S., RA Russo D., Filetti S.; RT "A Phe 486 thyrotropin receptor mutation in an autonomously functioning RT follicular carcinoma that was causing hyperthyroidism."; RL Thyroid 10:1009-1012(2000). RN [58] RP VARIANT HTNA VAL-463. RX PubMed=11201847; DOI=10.1089/thy.2000.10.1035; RA Fuhrer D., Warner J., Sequeira M., Paschke R., Gregory J.W., Ludgate M.; RT "Novel TSHR germline mutation (Met463Val) masquerading as Graves' disease RT in a large Welsh kindred with hyperthyroidism."; RL Thyroid 10:1035-1041(2000). RN [59] RP VARIANT HTNA PHE-597, AND CHARACTERIZATION OF VARIANT HTNA PHE-597. RX PubMed=11517004; DOI=10.1530/eje.0.1450249; RA Alberti L., Proverbio M.C., Costagliola S., Weber G., Beck-Peccoz P., RA Chiumello G., Persani L.; RT "A novel germline mutation in the TSH receptor gene causes non-autoimmune RT autosomal dominant hyperthyroidism."; RL Eur. J. Endocrinol. 145:249-254(2001). RN [60] RP VARIANT HTNA SER-431, AND CHARACTERIZATION OF VARIANT HTNA SER-431. RX PubMed=11549687; DOI=10.1210/jcem.86.9.7888; RA Biebermann H., Schoeneberg T., Hess C., Germak J., Gudermann T., RA Grueters A.; RT "The first activating TSH receptor mutation in transmembrane domain 1 RT identified in a family with nonautoimmune hyperthyroidism."; RL J. Clin. Endocrinol. Metab. 86:4429-4433(2001). RN [61] RP VARIANTS ASN-281; ILE-425; THR-453; PHE-486; ASN-505; ARG-512; GLN-512; RP THR-568; GLY-619; VAL-623; LEU-631; ALA-632; ILE-632; GLU-633; HIS-633; RP TYR-633; ALA-639 AND PHE-656, AND CHARACTERIZATION OF VARIANTS ILE-425 AND RP GLN-512. RX PubMed=11434721; DOI=10.1007/s001090000170; RA Truelzsch B., Krohn K., Wonerow P., Chey S., Holzapfel H.-P., Ackermann F., RA Fuehrer D., Paschke R.; RT "Detection of thyroid-stimulating hormone receptor and G(s)alpha mutations: RT in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis."; RL J. Mol. Med. 78:684-691(2001). RN [62] RP VARIANTS CHNG1 HIS-450 AND SER-498. RX PubMed=11442002; DOI=10.1089/105072501750302859; RA Nagashima T., Murakami M., Onigata K., Morimura T., Nagashima K., Mori M., RA Morikawa A.; RT "Novel inactivating missense mutations in the thyrotropin receptor gene in RT Japanese children with resistance to thyrotropin."; RL Thyroid 11:551-559(2001). RN [63] RP VARIANTS HYPERTHYROIDISM THR-453; MET-486; ARG-512 AND ALA-632. RX PubMed=12213664; DOI=10.1530/eje.0.1470287; RA Vanvooren V., Uchino S., Duprez L., Costa M.J., Vandekerckhove J., RA Parma J., Vassart G., Dumont J.E., van Sande J., Noguchi S.; RT "Oncogenic mutations in the thyrotropin receptor of autonomously RT functioning thyroid nodules in the Japanese population."; RL Eur. J. Endocrinol. 147:287-291(2002). RN [64] RP VARIANTS CHNG1 SER-41; ALA-162; PRO-467 AND ARG-600. RX PubMed=12050212; DOI=10.1210/jcem.87.6.8536; RA Alberti L., Proverbio M.C., Costagliola S., Romoli R., Boldrighini B., RA Vigone M.C., Weber G., Chiumello G., Beck-Peccoz P., Persani L.; RT "Germline mutations of TSH receptor gene as cause of nonautoimmune RT subclinical hypothyroidism."; RL J. Clin. Endocrinol. Metab. 87:2549-2555(2002). RN [65] RP VARIANT TOXIC THYROID ADENOMA ASN-593, VARIANT GLU-727, CHARACTERIZATION OF RP VARIANT TOXIC THYROID ADENOMA ASN-593, AND CHARACTERIZATION OF VARIANT RP GLU-727. RX PubMed=12589819; DOI=10.1016/s0006-291x(03)00071-8; RA Sykiotis G.P., Neumann S., Georgopoulos N.A., Sgourou A., RA Papachatzopoulou A., Markou K.B., Kyriazopoulou V., Paschke R., RA Vagenakis A.G., Papavassiliou A.G.; RT "Functional significance of the thyrotropin receptor germline polymorphism RT D727E."; RL Biochem. Biophys. Res. Commun. 301:1051-1056(2003). RN [66] RP VARIANTS HIS-36; THR-52 AND GLU-727, AND ASSOCIATION WITH PLASMA TSH LEVEL. RX PubMed=12788902; DOI=10.1210/jc.2002-021592; RA Peeters R.P., van Toor H., Klootwijk W., de Rijke Y.B., Kuiper G.G.J.M., RA Uitterlinden A.G., Visser T.J.; RT "Polymorphisms in thyroid hormone pathway genes are associated with plasma RT TSH and iodothyronine levels in healthy subjects."; RL J. Clin. Endocrinol. Metab. 88:2880-2888(2003). RN [67] RP VARIANTS HIS-36 AND THR-52, AND RECEPTOR GENETIC ANALYSIS IN CHILDREN WITH RP DOWN'S SYNDROME. RX PubMed=14759073; DOI=10.1007/bf03348198; RA Tonacchera M., Perri A., De Marco G., Agretti P., Montanelli L., RA Banco M.E., Corrias A., Bellone J., Tosi M.T., Vitti P., Martino E., RA Pinchera A., Chiovato L.; RT "TSH receptor and Gs(alpha) genetic analysis in children with Down's RT syndrome and subclinical hypothyroidism."; RL J. Endocrinol. Invest. 26:997-1000(2003). RN [68] RP VARIANT CHNG1 THR-553. RX PubMed=14725684; DOI=10.1111/j.1365-2265.2004.01967.x; RA Park S.-M., Clifton-Bligh R.J., Betts P., Chatterjee V.K.K.; RT "Congenital hypothyroidism and apparent athyreosis with compound RT heterozygosity or compensated hypothyroidism with probable hemizygosity for RT inactivating mutations of the TSH receptor."; RL Clin. Endocrinol. (Oxf.) 60:220-227(2004). RN [69] RP VARIANT HTNA ASN-505. RX PubMed=15163335; DOI=10.1111/j.1365-2265.2004.02040.x; RA Vaidya B., Campbell V., Tripp J.H., Spyer G., Hattersley A.T., Ellard S.; RT "Premature birth and low birth weight associated with nonautoimmune RT hyperthyroidism due to an activating thyrotropin receptor gene mutation."; RL Clin. Endocrinol. (Oxf.) 60:711-718(2004). RN [70] RP VARIANTS CHNG1 ALA-162 AND PRO-252, AND CHARACTERIZATION OF VARIANT CHNG1 RP PRO-252. RX PubMed=15531543; DOI=10.1210/jc.2004-1243; RA Tonacchera M., Perri A., De Marco G., Agretti P., Banco M.E., Di Cosmo C., RA Grasso L., Vitti P., Chiovato L., Pinchera A.; RT "Low prevalence of thyrotropin receptor mutations in a large series of RT subjects with sporadic and familial nonautoimmune subclinical RT hypothyroidism."; RL J. Clin. Endocrinol. Metab. 89:5787-5793(2004). RN [71] RP VARIANTS CHNG1 ALA-162; ASP-432 AND LEU-449, AND CHARACTERIZATION OF RP VARIANTS CHNG1 ASP-432 AND LEU-449. RX PubMed=25978107; DOI=10.1210/jc.2014-4511; RA Labadi A., Grassi E.S., Gellen B., Kleinau G., Biebermann H., Ruzsa B., RA Gelmini G., Rideg O., Miseta A., Kovacs G.L., Patocs A., Felszeghy E., RA Nagy E.V., Mezosi E., Persani L.; RT "Loss-of-function variants in a Hungarian cohort reveal structural insights RT on TSH receptor maturation and signaling."; RL J. Clin. Endocrinol. Metab. 100:E1039-E1045(2015). CC -!- FUNCTION: Receptor for the thyroid-stimulating hormone (TSH) or CC thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor CC for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or CC thyrostimulin (PubMed:12045258). The activity of this receptor is CC mediated by G proteins which activate adenylate cyclase CC (PubMed:11847099). Plays a central role in controlling thyroid cell CC metabolism (By similarity). {ECO:0000250|UniProtKB:P21463, CC ECO:0000269|PubMed:11847099, ECO:0000269|PubMed:12045258}. CC -!- SUBUNIT: Interacts with heterodimer GPHA2:GPHB5; this interaction CC stimulates cAMP production (PubMed:12045258). Interacts (via the PDZ- CC binding motif) with SCRIB; regulates TSHR trafficking and function CC (PubMed:15775968). {ECO:0000269|PubMed:12045258, CC ECO:0000269|PubMed:15775968}. CC -!- INTERACTION: CC P16473; P30542: ADORA1; NbExp=2; IntAct=EBI-13939599, EBI-2903663; CC P16473; Q9NPA3: MID1IP1; NbExp=2; IntAct=EBI-13939599, EBI-750096; CC P16473; Q14160: SCRIB; NbExp=3; IntAct=EBI-13939599, EBI-357345; CC P16473; P21579: SYT1; NbExp=2; IntAct=EBI-13939599, EBI-524909; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11847099}; CC Multi-pass membrane protein {ECO:0000305}. Basolateral cell membrane CC {ECO:0000269|PubMed:11847099}; Multi-pass membrane protein CC {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional isoforms seem to exist.; CC Name=Long; CC IsoId=P16473-1; Sequence=Displayed; CC Name=Short; CC IsoId=P16473-2; Sequence=VSP_001981, VSP_001982; CC Name=3; CC IsoId=P16473-3; Sequence=VSP_044643, VSP_044644; CC -!- TISSUE SPECIFICITY: Expressed in thyroide cells (at protein level) CC (PubMed:11847099). Expressed in the thyroid (PubMed:2610690). CC {ECO:0000269|PubMed:11847099, ECO:0000269|PubMed:2610690}. CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:11847099}. CC -!- PTM: Sulfated. Sulfation on Tyr-385 plays a role in thyrotropin CC receptor binding and activation. {ECO:0000269|PubMed:11847099}. CC -!- POLYMORPHISM: The Asp727Glu polymorphism is associated with Graves CC disease in a Russian population. The Glu727 allele and the heterozygous CC Asp727Glu genotype are related to higher risk of the disease. The CC Asp727Glu polymorphism significantly ameliorates G(s)alpha protein CC activation in the presence of the gain-of-function mutation Ala593Asn CC although it is functionally inert in the context of the wild-type TSHR. CC {ECO:0000269|PubMed:11887032}. CC -!- DISEASE: Note=Defects in TSHR are found in patients affected by CC hyperthyroidism with different etiologies. Somatic, constitutively CC activating TSHR mutations and/or constitutively activating G(s)alpha CC mutations have been identified in toxic thyroid nodules (TTNs) that are CC the predominant cause of hyperthyroidism in iodine deficient areas. CC These mutations lead to TSH independent activation of the cAMP cascade CC resulting in thyroid growth and hormone production. TSHR mutations are CC found in autonomously functioning thyroid nodules (AFTN), toxic CC multinodular goiter (TMNG) and hyperfunctioning thyroid adenomas (HTA). CC TMNG encompasses a spectrum of different clinical entities, ranging CC from a single hyperfunctioning nodule within an enlarged thyroid, to CC multiple hyperfunctioning areas scattered throughout the gland. HTA are CC discrete encapsulated neoplasms characterized by TSH-independent CC autonomous growth, hypersecretion of thyroid hormones, and TSH CC suppression. Defects in TSHR are also a cause of thyroid neoplasms CC (papillary and follicular cancers). CC -!- DISEASE: Note=Autoantibodies against TSHR are directly responsible for CC the pathogenesis and hyperthyroidism of Graves disease. Antibody CC interaction with TSHR results in an uncontrolled receptor stimulation. CC -!- DISEASE: Hypothyroidism, congenital, non-goitrous, 1 (CHNG1) CC [MIM:275200]: A non-autoimmune condition characterized by resistance to CC thyroid-stimulating hormone (TSH) leading to increased levels of plasma CC TSH and low levels of thyroid hormone. It presents variable severity CC depending on the completeness of the defect. Most patients are CC euthyroid and asymptomatic, with a normal sized thyroid gland. Only a CC subset of patients develop hypothyroidism and present a hypoplastic CC thyroid gland. {ECO:0000269|PubMed:10720030, CC ECO:0000269|PubMed:11095460, ECO:0000269|PubMed:11442002, CC ECO:0000269|PubMed:12050212, ECO:0000269|PubMed:14725684, CC ECO:0000269|PubMed:15531543, ECO:0000269|PubMed:25978107, CC ECO:0000269|PubMed:7528344, ECO:0000269|PubMed:8954020, CC ECO:0000269|PubMed:9100579, ECO:0000269|PubMed:9185526, CC ECO:0000269|PubMed:9329388}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Familial gestational hyperthyroidism (HTFG) [MIM:603373]: A CC condition characterized by abnormally high levels of serum thyroid CC hormones occurring during early pregnancy. CC {ECO:0000269|PubMed:9854118}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hyperthyroidism, non-autoimmune (HTNA) [MIM:609152]: A CC condition characterized by abnormally high levels of serum thyroid CC hormones, thyroid hyperplasia, goiter and lack of anti-thyroid CC antibodies. Typical features of Graves disease such as exophthalmia, CC myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of CC the thyroid gland are absent. {ECO:0000269|PubMed:10199795, CC ECO:0000269|PubMed:10852462, ECO:0000269|PubMed:11081252, CC ECO:0000269|PubMed:11127522, ECO:0000269|PubMed:11201847, CC ECO:0000269|PubMed:11517004, ECO:0000269|PubMed:11549687, CC ECO:0000269|PubMed:15163335, ECO:0000269|PubMed:7800007, CC ECO:0000269|PubMed:7920658, ECO:0000269|PubMed:8636266, CC ECO:0000269|PubMed:8964822, ECO:0000269|PubMed:9349581, CC ECO:0000269|PubMed:9360555, ECO:0000269|PubMed:9398746, CC ECO:0000269|PubMed:9589634}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC FSH/LSH/TSH subfamily. {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA70232.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=TSH receptor database; CC URL="https://endokrinologie.uniklinikum-leipzig.de/tsh/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=TSH receptor entry; CC URL="https://en.wikipedia.org/wiki/TSH_receptor"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/290/TSHR"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M31774; AAA36783.1; -; mRNA. DR EMBL; M32215; AAA61236.1; -; mRNA. DR EMBL; M73747; AAA70232.1; ALT_FRAME; mRNA. DR EMBL; S45272; AAB23390.2; -; mRNA. DR EMBL; S49816; AAB24246.1; -; mRNA. DR EMBL; AY429111; AAR07906.1; -; mRNA. DR EMBL; AC007262; AAD31568.1; -; Genomic_DNA. DR EMBL; AC010072; AAF09032.1; -; Genomic_DNA. DR EMBL; AC010582; AAF26775.1; -; Genomic_DNA. DR EMBL; AL136040; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009237; AAH09237.1; -; mRNA. DR EMBL; BC024205; AAH24205.1; -; mRNA. DR EMBL; BC063613; AAH63613.1; -; mRNA. DR EMBL; BC108653; AAI08654.1; -; mRNA. DR EMBL; BC120973; AAI20974.1; -; mRNA. DR EMBL; BC127628; AAI27629.1; -; mRNA. DR EMBL; BC141970; AAI41971.1; -; mRNA. DR CCDS; CCDS32131.1; -. [P16473-2] DR CCDS; CCDS55935.1; -. [P16473-3] DR CCDS; CCDS9872.1; -. [P16473-1] DR PIR; A33789; QRHURH. DR PIR; JC1319; JC1319. DR PIR; T01787; T01787. DR RefSeq; NP_000360.2; NM_000369.2. DR RefSeq; NP_001018046.1; NM_001018036.2. [P16473-2] DR RefSeq; NP_001136098.1; NM_001142626.2. [P16473-3] DR RefSeq; XP_005268096.1; XM_005268039.1. DR RefSeq; XP_006720308.1; XM_006720245.1. DR PDB; 2XWT; X-ray; 1.90 A; C=22-260. DR PDB; 3G04; X-ray; 2.55 A; C=22-260. DR PDB; 7T9M; EM; 3.10 A; R=22-764. DR PDB; 7XW5; EM; 2.96 A; R=21-764. DR PDB; 7XW6; EM; 2.78 A; R=21-764. DR PDB; 7XW7; EM; 5.50 A; R=21-764. DR PDBsum; 2XWT; -. DR PDBsum; 3G04; -. DR PDBsum; 7T9M; -. DR PDBsum; 7XW5; -. DR PDBsum; 7XW6; -. DR PDBsum; 7XW7; -. DR AlphaFoldDB; P16473; -. DR EMDB; EMD-25762; -. DR EMDB; EMD-27640; -. DR EMDB; EMD-33491; -. DR EMDB; EMD-33492; -. DR EMDB; EMD-33493; -. DR SMR; P16473; -. DR BioGRID; 113104; 109. DR IntAct; P16473; 25. DR MINT; P16473; -. DR STRING; 9606.ENSP00000441235; -. DR BindingDB; P16473; -. DR ChEMBL; CHEMBL1963; -. DR DrugBank; DB00024; Thyrotropin alfa. DR DrugCentral; P16473; -. DR GuidetoPHARMACOLOGY; 255; -. DR TCDB; 9.A.14.1.21; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P16473; 6 sites, No reported glycans. DR GlyGen; P16473; 6 sites. DR iPTMnet; P16473; -. DR PhosphoSitePlus; P16473; -. DR SwissPalm; P16473; -. DR BioMuta; TSHR; -. DR DMDM; 62298994; -. DR MassIVE; P16473; -. DR PaxDb; 9606-ENSP00000441235; -. DR PeptideAtlas; P16473; -. DR ProteomicsDB; 24847; -. DR ProteomicsDB; 32578; -. DR ProteomicsDB; 53374; -. [P16473-1] DR ProteomicsDB; 53375; -. [P16473-2] DR ABCD; P16473; 14 sequenced antibodies. DR Antibodypedia; 4379; 1253 antibodies from 38 providers. DR DNASU; 7253; -. DR Ensembl; ENST00000342443.10; ENSP00000340113.6; ENSG00000165409.18. [P16473-2] DR Ensembl; ENST00000554435.1; ENSP00000450549.1; ENSG00000165409.18. [P16473-3] DR GeneID; 7253; -. DR KEGG; hsa:7253; -. DR UCSC; uc001xvc.4; human. [P16473-1] DR AGR; HGNC:12373; -. DR CTD; 7253; -. DR DisGeNET; 7253; -. DR GeneCards; TSHR; -. DR HGNC; HGNC:12373; TSHR. DR HPA; ENSG00000165409; Tissue enriched (thyroid). DR MalaCards; TSHR; -. DR MIM; 275200; phenotype. DR MIM; 603372; gene+phenotype. DR MIM; 603373; phenotype. DR MIM; 609152; phenotype. DR neXtProt; NX_P16473; -. DR OpenTargets; ENSG00000165409; -. DR Orphanet; 95713; Athyreosis. DR Orphanet; 99819; Familial gestational hyperthyroidism. DR Orphanet; 424; Familial hyperthyroidism due to mutations in TSH receptor. DR Orphanet; 90673; Hypothyroidism due to TSH receptor mutations. DR Orphanet; 95720; Thyroid hypoplasia. DR PharmGKB; PA37042; -. DR VEuPathDB; HostDB:ENSG00000165409; -. DR eggNOG; KOG2087; Eukaryota. DR GeneTree; ENSGT00940000156510; -. DR InParanoid; P16473; -. DR OrthoDB; 1202285at2759; -. DR PhylomeDB; P16473; -. DR TreeFam; TF316814; -. DR PathwayCommons; P16473; -. DR Reactome; R-HSA-375281; Hormone ligand-binding receptors. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR SignaLink; P16473; -. DR SIGNOR; P16473; -. DR BioGRID-ORCS; 7253; 11 hits in 1154 CRISPR screens. DR ChiTaRS; TSHR; human. DR EvolutionaryTrace; P16473; -. DR GeneWiki; Thyrotropin_receptor; -. DR GenomeRNAi; 7253; -. DR Pharos; P16473; Tclin. DR PRO; PR:P16473; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P16473; Protein. DR Bgee; ENSG00000165409; Expressed in left lobe of thyroid gland and 109 other cell types or tissues. DR ExpressionAtlas; P16473; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central. DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; IMP:UniProtKB. DR GO; GO:0004996; F:thyroid-stimulating hormone receptor activity; IMP:UniProtKB. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:1904588; P:cellular response to glycoprotein; IMP:UniProtKB. DR GO; GO:1905229; P:cellular response to thyrotropin-releasing hormone; IMP:UniProtKB. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc. DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0038194; P:thyroid-stimulating hormone signaling pathway; IMP:UniProtKB. DR CDD; cd15964; 7tmA_TSH-R; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR002131; Gphrmn_rcpt_fam. DR InterPro; IPR026906; LRR_5. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR002274; TSH_rcpt. DR PANTHER; PTHR24372; GLYCOPROTEIN HORMONE RECEPTOR; 1. DR PANTHER; PTHR24372:SF0; THYROTROPIN RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR Pfam; PF13306; LRR_5; 2. DR PRINTS; PR00373; GLYCHORMONER. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR01145; TSHRECEPTOR. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P16473; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; KW Congenital hypothyroidism; Direct protein sequencing; Disease variant; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; KW Leucine-rich repeat; Membrane; Receptor; Reference proteome; Repeat; KW Signal; Sulfation; Transducer; Transmembrane; Transmembrane helix. FT SIGNAL 1..20 FT CHAIN 21..764 FT /note="Thyrotropin receptor" FT /id="PRO_0000012786" FT TOPO_DOM 21..413 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 414..441 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 442..450 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 451..473 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 474..494 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 495..517 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 518..537 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 538..560 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 561..580 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 581..602 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 603..625 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 626..649 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 650..660 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 661..682 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 683..764 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 100..124 FT /note="LRR 1" FT REPEAT 125..150 FT /note="LRR 2" FT REPEAT 152..174 FT /note="LRR 3" FT REPEAT 176..199 FT /note="LRR 4" FT REPEAT 200..223 FT /note="LRR 5" FT REPEAT 227..248 FT /note="LRR 6" FT REPEAT 250..271 FT /note="LRR 7" FT MOTIF 762..764 FT /note="PDZ-binding" FT MOD_RES 385 FT /note="Sulfotyrosine" FT /evidence="ECO:0000305|PubMed:11847099" FT CARBOHYD 77 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11502179, FT ECO:0000269|PubMed:17542669" FT CARBOHYD 99 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17542669" FT CARBOHYD 113 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11502179, FT ECO:0000269|PubMed:17542669" FT CARBOHYD 177 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17542669" FT CARBOHYD 198 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11502179, FT ECO:0000269|PubMed:17542669" FT CARBOHYD 302 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11502179" FT DISULFID 31..41 FT DISULFID 494..569 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VAR_SEQ 232..274 FT /note="DVSQTSVTALPSKGLEHLKELIARNTWTLKKLPLSLSFLHLTR -> VENVA FT VSGKGFCKSLFSWLYRLPLGRKSLSFETQKAPRSSMPS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_044643" FT VAR_SEQ 232..253 FT /note="DVSQTSVTALPSKGLEHLKELI -> LPLGRKSLSFETQKAPRSSMPS (in FT isoform Short)" FT /evidence="ECO:0000303|PubMed:1445355, FT ECO:0000303|PubMed:1530609, ECO:0000303|PubMed:15489334" FT /id="VSP_001981" FT VAR_SEQ 254..764 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:1445355, FT ECO:0000303|PubMed:1530609, ECO:0000303|PubMed:15489334" FT /id="VSP_001982" FT VAR_SEQ 275..764 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_044644" FT VARIANT 34 FT /note="E -> K (in dbSNP:rs45499704)" FT /id="VAR_055925" FT VARIANT 36 FT /note="D -> H (in a patient with Graves disease; FT dbSNP:rs61747482)" FT /evidence="ECO:0000269|PubMed:12788902, FT ECO:0000269|PubMed:12930595, ECO:0000269|PubMed:14759073, FT ECO:0000269|PubMed:1955520, ECO:0000269|PubMed:7556878" FT /id="VAR_003564" FT VARIANT 41 FT /note="C -> S (in CHNG1)" FT /evidence="ECO:0000269|PubMed:12050212, FT ECO:0000269|PubMed:8954020" FT /id="VAR_011519" FT VARIANT 52 FT /note="P -> T (does not contribute to the genetic FT susceptibility to Graves disease; dbSNP:rs2234919)" FT /evidence="ECO:0000269|PubMed:10651846, FT ECO:0000269|PubMed:12788902, ECO:0000269|PubMed:12930595, FT ECO:0000269|PubMed:14759073, ECO:0000269|PubMed:7488864, FT ECO:0000269|PubMed:7508946, ECO:0000269|PubMed:7528344" FT /id="VAR_003565" FT VARIANT 109 FT /note="R -> Q (in CHNG1)" FT /evidence="ECO:0000269|PubMed:9100579" FT /id="VAR_011520" FT VARIANT 162 FT /note="P -> A (in CHNG1; dbSNP:rs121908863)" FT /evidence="ECO:0000269|PubMed:12050212, FT ECO:0000269|PubMed:15531543, ECO:0000269|PubMed:25978107, FT ECO:0000269|PubMed:7528344, ECO:0000269|PubMed:8954020" FT /id="VAR_011521" FT VARIANT 167 FT /note="I -> N (in CHNG1)" FT /evidence="ECO:0000269|PubMed:7528344" FT /id="VAR_011522" FT VARIANT 183 FT /note="K -> R (in HTFG; enhances receptor response to FT chorionic gonadotropin)" FT /evidence="ECO:0000269|PubMed:9854118" FT /id="VAR_003566" FT VARIANT 197 FT /note="F -> I (in papillary cancer)" FT /evidence="ECO:0000269|PubMed:7647578" FT /id="VAR_003567" FT VARIANT 219 FT /note="D -> E (in papillary cancer)" FT /evidence="ECO:0000269|PubMed:7647578" FT /id="VAR_003568" FT VARIANT 252 FT /note="L -> P (in CHNG1; displays a low expression at the FT cell surface and a reduced response to bovine TSH in terms FT of cAMP production)" FT /evidence="ECO:0000269|PubMed:15531543" FT /id="VAR_021495" FT VARIANT 281 FT /note="S -> I (in hyperthyroidism; congenital; due to a FT toxic adenoma)" FT /evidence="ECO:0000269|PubMed:9294132" FT /id="VAR_003569" FT VARIANT 281 FT /note="S -> N (in HTNA; gain of function; found in toxic FT thyroid nodules and hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:10852462, FT ECO:0000269|PubMed:11127522, ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:9253356, ECO:0000269|PubMed:9589634" FT /id="VAR_003570" FT VARIANT 281 FT /note="S -> T (in hyperthyroidism; found in FT hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:9253356" FT /id="VAR_011523" FT VARIANT 310 FT /note="R -> C (in CHNG1)" FT /evidence="ECO:0000269|PubMed:11095460" FT /id="VAR_011524" FT VARIANT 390 FT /note="C -> W (in CHNG1; persistent hypothyroidism and FT defective thyroid development; abolishes high affinity FT hormone binding)" FT /evidence="ECO:0000269|PubMed:8954020, FT ECO:0000269|PubMed:9329388" FT /id="VAR_011525" FT VARIANT 410 FT /note="D -> N (in CHNG1; lack of adenylate cyclase FT activation)" FT /evidence="ECO:0000269|PubMed:8954020" FT /id="VAR_011526" FT VARIANT 425 FT /note="S -> I (found in toxic thyroid nodules; 8 to 9 times FT higher levels of basal cAMP than wild-type TSHR and similar FT response to maximal TSH stimulation)" FT /evidence="ECO:0000269|PubMed:11434721" FT /id="VAR_021496" FT VARIANT 431 FT /note="G -> S (in HTNA; gain of function; constitutive FT activation of the G(s)/adenylyl cyclase system)" FT /evidence="ECO:0000269|PubMed:11127522, FT ECO:0000269|PubMed:11549687" FT /id="VAR_011527" FT VARIANT 432 FT /note="N -> D (in CHNG1; abolishes cell membrane location; FT abolishes adenylate cyclase-activating G-protein coupled FT receptor signaling pathway; abolishes phospholipase FT C-activating G-protein coupled receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:25978107" FT /id="VAR_075585" FT VARIANT 449 FT /note="P -> L (in CHNG1; no effect on cell membrane FT location; upon TSH stimulation decreases more phospholipase FT C-activating G-protein coupled receptor signaling pathway FT than adenylate cyclase-activating G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:25978107" FT /id="VAR_075586" FT VARIANT 450 FT /note="R -> H (in CHNG1)" FT /evidence="ECO:0000269|PubMed:11442002" FT /id="VAR_011528" FT VARIANT 453 FT /note="M -> T (in HTNA; sporadic; found in toxic thyroid FT nodules and hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:12213664, ECO:0000269|PubMed:8964822, FT ECO:0000269|PubMed:9253356" FT /id="VAR_011529" FT VARIANT 463 FT /note="M -> V (in HTNA; gain of function)" FT /evidence="ECO:0000269|PubMed:11201847" FT /id="VAR_011530" FT VARIANT 467 FT /note="L -> P (in CHNG1)" FT /evidence="ECO:0000269|PubMed:12050212" FT /id="VAR_017295" FT VARIANT 477 FT /note="T -> I (in CHNG1; severe hypothyroidism)" FT /evidence="ECO:0000269|PubMed:10720030" FT /id="VAR_017296" FT VARIANT 486 FT /note="I -> F (in HTNA; found in thyroid toxic nodules and FT hyperfunctioning thyroid adenomas; also in hyperfunctioning FT follicular carcinoma)" FT /evidence="ECO:0000269|PubMed:10852462, FT ECO:0000269|PubMed:11128715, ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:9253356" FT /id="VAR_011531" FT VARIANT 486 FT /note="I -> M (in HTNA; found in hyperfunctioning thyroid FT adenomas)" FT /evidence="ECO:0000269|PubMed:10852462, FT ECO:0000269|PubMed:12213664, ECO:0000269|PubMed:9253356" FT /id="VAR_011532" FT VARIANT 498 FT /note="G -> S (in CHNG1)" FT /evidence="ECO:0000269|PubMed:11442002" FT /id="VAR_011533" FT VARIANT 505 FT /note="S -> N (in HTNA; found in toxic thyroid nodules)" FT /evidence="ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:15163335, ECO:0000269|PubMed:9360555" FT /id="VAR_003571" FT VARIANT 505 FT /note="S -> R (in HTNA; gain of function)" FT /evidence="ECO:0000269|PubMed:8636266" FT /id="VAR_011534" FT VARIANT 509 FT /note="V -> A (in HTNA; gain of function)" FT /evidence="ECO:0000269|PubMed:7920658" FT /id="VAR_011535" FT VARIANT 512 FT /note="L -> Q (found in toxic thyroid nodules; 5 times FT higher levels of basal cAMP than wild-type TSHR and FT slightly less response to maximal TSH stimulation)" FT /evidence="ECO:0000269|PubMed:11434721" FT /id="VAR_021497" FT VARIANT 512 FT /note="L -> R (in hyperthyroidism; found in autonomously FT functioning thyroid nodules; 3.3-fold increase in basal FT cAMP level)" FT /evidence="ECO:0000269|PubMed:11022192, FT ECO:0000269|PubMed:11434721, ECO:0000269|PubMed:12213664" FT /id="VAR_011536" FT VARIANT 525 FT /note="F -> L (in CHNG1; impairs adenylate cyclase FT activation)" FT /evidence="ECO:0000269|PubMed:8954020" FT /id="VAR_011537" FT VARIANT 528 FT /note="R -> H" FT /evidence="ECO:0000269|PubMed:9589634" FT /id="VAR_003572" FT VARIANT 553 FT /note="A -> T (in CHNG1; severe hypothyroidism)" FT /evidence="ECO:0000269|PubMed:14725684, FT ECO:0000269|PubMed:9185526" FT /id="VAR_011538" FT VARIANT 568 FT /note="I -> T (in HTNA; found in thyroid toxic nodules and FT hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:11081252, FT ECO:0000269|PubMed:11434721, ECO:0000269|PubMed:9253356" FT /id="VAR_011539" FT VARIANT 593 FT /note="A -> N (in toxic thyroid adenoma; somatic mutation; FT constitutively activates the cAMP cascade; requires 2 FT nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:12589819" FT /id="VAR_021498" FT VARIANT 597 FT /note="V -> F (in HTNA; 11-fold increase in specific FT constitutive activity; decreased receptor protein FT expression)" FT /evidence="ECO:0000269|PubMed:11517004" FT /id="VAR_021499" FT VARIANT 597 FT /note="V -> L (in hyperthyroidism; congenital with severe FT thyrotoxicosis)" FT /evidence="ECO:0000269|PubMed:10560955" FT /id="VAR_011540" FT VARIANT 600 FT /note="C -> R (in CHNG1)" FT /evidence="ECO:0000269|PubMed:12050212" FT /id="VAR_017297" FT VARIANT 606 FT /note="I -> M" FT /evidence="ECO:0000269|PubMed:10487707" FT /id="VAR_011541" FT VARIANT 619 FT /note="D -> G (in hyperthyroidism; found in toxic thyroid FT nodules and hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:8413627, ECO:0000269|PubMed:9253356" FT /id="VAR_003573" FT VARIANT 623 FT /note="A -> I (in hyperthyroidism; found in FT hyperfunctioning thyroid adenomas; gain of function; FT requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:8413627, FT ECO:0000269|PubMed:9253356" FT /id="VAR_003574" FT VARIANT 623 FT /note="A -> V (in hyperthyroidism; found in toxic thyroid FT nodules and hyperfunctioning thyroid adenomas; gain of FT function)" FT /evidence="ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:7989485" FT /id="VAR_011542" FT VARIANT 629 FT /note="L -> F (in HTNA; also in hyperfunctioning thyroid FT adenomas and non-adenomatous nodules)" FT /evidence="ECO:0000269|PubMed:10852462, FT ECO:0000269|PubMed:9253356, ECO:0000269|PubMed:9398746" FT /id="VAR_003575" FT VARIANT 630 FT /note="I -> L (in hyperthyroidism; found in FT hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:9253356" FT /id="VAR_011543" FT VARIANT 631 FT /note="F -> C (in hyperthyroidism; found in FT hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:8045989" FT /id="VAR_011544" FT VARIANT 631 FT /note="F -> L (in HTNA; gain of function; found in toxic FT thyroid nodules and hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:7800007, ECO:0000269|PubMed:9253356" FT /id="VAR_011545" FT VARIANT 632 FT /note="T -> A (in HTNA; found in toxic thyroid nodules and FT hyperfunctioning non-adenomatous nodules)" FT /evidence="ECO:0000269|PubMed:10852462, FT ECO:0000269|PubMed:11434721, ECO:0000269|PubMed:12213664" FT /id="VAR_011546" FT VARIANT 632 FT /note="T -> I (in HTNA; gain of function; found in thyroid FT toxic nodules and hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:10852462, FT ECO:0000269|PubMed:11127522, ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:7989485, ECO:0000269|PubMed:8045989, FT ECO:0000269|PubMed:9253356, ECO:0000269|PubMed:9349581" FT /id="VAR_011547" FT VARIANT 633 FT /note="D -> A (in hyperthyroidism; found in FT hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:9253356" FT /id="VAR_011548" FT VARIANT 633 FT /note="D -> E (in HTNA; found in thyroid toxic nodules and FT hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:10852462, FT ECO:0000269|PubMed:11434721, ECO:0000269|PubMed:8045989, FT ECO:0000269|PubMed:9253356" FT /id="VAR_011549" FT VARIANT 633 FT /note="D -> H (in hyperthyroidism; found in toxic thyroid FT nodules and hyperfunctioning thyroid adenomas; also found FT in hyperfunctioning insular carcinoma; gain of function; FT dbSNP:rs28937584)" FT /evidence="ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:9062474, ECO:0000269|PubMed:9253356" FT /id="VAR_011550" FT VARIANT 633 FT /note="D -> Y (in hyperthyroidism; found in toxic thyroid FT nodules and hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:11434721, FT ECO:0000269|PubMed:8045989, ECO:0000269|PubMed:9253356" FT /id="VAR_011551" FT VARIANT 639 FT /note="P -> A (found in toxic thyroid nodules)" FT /evidence="ECO:0000269|PubMed:11434721" FT /id="VAR_021500" FT VARIANT 639 FT /note="P -> S (in HTNA; gain of function)" FT /evidence="ECO:0000269|PubMed:10199795" FT /id="VAR_011552" FT VARIANT 647 FT /note="A -> V (in HTNA; found in non-adenomatous FT hyperfunctioning nodules)" FT /evidence="ECO:0000269|PubMed:10852462" FT /id="VAR_011553" FT VARIANT 650 FT /note="N -> Y (in HTNA; gain of function)" FT /evidence="ECO:0000269|PubMed:8636266" FT /id="VAR_011554" FT VARIANT 656 FT /note="V -> F (found in toxic thyroid nodules)" FT /evidence="ECO:0000269|PubMed:11434721" FT /id="VAR_021501" FT VARIANT 658..661 FT /note="Missing (in hyperthyroidism; found in FT hyperfunctioning thyroid adenomas)" FT /evidence="ECO:0000269|PubMed:9253356" FT /id="VAR_011555" FT VARIANT 670 FT /note="N -> S (in HTNA; gain of function)" FT /evidence="ECO:0000269|PubMed:8636266" FT /id="VAR_011556" FT VARIANT 672 FT /note="C -> Y (in HTNA; gain of function)" FT /evidence="ECO:0000269|PubMed:7920658" FT /id="VAR_011557" FT VARIANT 677 FT /note="L -> V (in thyroid carcinoma; with thyrotoxicosis; FT gain of function)" FT /evidence="ECO:0000269|PubMed:10037070" FT /id="VAR_011558" FT VARIANT 703 FT /note="A -> G" FT /evidence="ECO:0000269|PubMed:10487707" FT /id="VAR_011559" FT VARIANT 715 FT /note="N -> D (in papillary cancer)" FT /evidence="ECO:0000269|PubMed:7647578" FT /id="VAR_003576" FT VARIANT 720 FT /note="Q -> E" FT /evidence="ECO:0000269|PubMed:10487707" FT /id="VAR_011560" FT VARIANT 723 FT /note="K -> M (in papillary cancer)" FT /evidence="ECO:0000269|PubMed:7647578" FT /id="VAR_003577" FT VARIANT 727 FT /note="D -> E (may be a predisposing factor in toxic FT multinodular goiter pathogenesis; activation of the cAMP FT cascade does not differ from the wild-type; FT dbSNP:rs1991517)" FT /evidence="ECO:0000269|PubMed:10487707, FT ECO:0000269|PubMed:10946859, ECO:0000269|PubMed:12508121, FT ECO:0000269|PubMed:12589819, ECO:0000269|PubMed:12788902, FT ECO:0000269|PubMed:2302212, ECO:0000269|PubMed:7647578" FT /id="VAR_003578" FT MUTAGEN 283 FT /note="C->S: Abolishes cell surface expression." FT /evidence="ECO:0000269|PubMed:11847099" FT MUTAGEN 385..387 FT /note="YDY->EDE: Inhibits intracellular cAMP accumulation." FT /evidence="ECO:0000269|PubMed:11847099" FT MUTAGEN 385..387 FT /note="YDY->FDF: Abolishes sulfation. Inhibits FT intracellular cAMP accumulation." FT /evidence="ECO:0000269|PubMed:11847099" FT MUTAGEN 385 FT /note="Y->E: Reduces binding with thyrotropin. Inhibits FT intracellular cAMP accumulation." FT /evidence="ECO:0000269|PubMed:11847099, FT ECO:0000305|PubMed:11847099" FT MUTAGEN 385 FT /note="Y->F: Reduces sulfation. Reduces binding with FT thyrotropin. Inhibits intracellular cAMP accumulation." FT /evidence="ECO:0000269|PubMed:11847099, FT ECO:0000305|PubMed:11847099" FT MUTAGEN 387 FT /note="Y->E: No change in intracellular cAMP accumulation." FT /evidence="ECO:0000269|PubMed:11847099" FT MUTAGEN 387 FT /note="Y->F: Reduces sulfation. No change in intracellular FT cAMP accumulation." FT /evidence="ECO:0000269|PubMed:11847099" FT CONFLICT 87 FT /note="V -> L (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 196..198 FT /note="AFN -> DFF (in Ref. 4; AAA70232)" FT /evidence="ECO:0000305" FT CONFLICT 257 FT /note="T -> S (in Ref. 4; AAA70232)" FT /evidence="ECO:0000305" FT CONFLICT 264 FT /note="P -> A (in Ref. 4; AAA70232)" FT /evidence="ECO:0000305" FT CONFLICT 306..308 FT /note="MQS -> IET (in Ref. 4; AAA70232)" FT /evidence="ECO:0000305" FT CONFLICT 528 FT /note="R -> A (in Ref. 4; AAA70232)" FT /evidence="ECO:0000305" FT CONFLICT 601 FT /note="Y -> H (in Ref. 1; AAA36783)" FT /evidence="ECO:0000305" FT CONFLICT 635 FT /note="I -> T (in Ref. 4; AAA70232)" FT /evidence="ECO:0000305" FT CONFLICT 645 FT /note="L -> V (in Ref. 4; AAA70232)" FT /evidence="ECO:0000305" FT CONFLICT 669 FT /note="L -> I (in Ref. 4; AAA70232)" FT /evidence="ECO:0000305" FT CONFLICT 744 FT /note="N -> K (in Ref. 3; AAA61236)" FT /evidence="ECO:0000305" FT STRAND 26..28 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 30..33 FT /evidence="ECO:0007829|PDB:2XWT" FT TURN 35..37 FT /evidence="ECO:0007829|PDB:3G04" FT STRAND 38..41 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 56..61 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:2XWT" FT TURN 69..74 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 80..84 FT /evidence="ECO:0007829|PDB:2XWT" FT TURN 94..96 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 97..99 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 105..111 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 121..123 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 130..136 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 152..160 FT /evidence="ECO:0007829|PDB:2XWT" FT TURN 169..174 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 175..183 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 190..192 FT /evidence="ECO:0007829|PDB:3G04" FT TURN 194..199 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 201..206 FT /evidence="ECO:0007829|PDB:2XWT" FT TURN 218..223 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 229..232 FT /evidence="ECO:0007829|PDB:2XWT" FT STRAND 243..245 FT /evidence="ECO:0007829|PDB:7XW6" FT STRAND 250..253 FT /evidence="ECO:0007829|PDB:2XWT" FT HELIX 266..269 FT /evidence="ECO:0007829|PDB:7XW6" FT STRAND 274..276 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 282..289 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 383..388 FT /evidence="ECO:0007829|PDB:7XW5" FT STRAND 397..400 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 415..429 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 432..441 FT /evidence="ECO:0007829|PDB:7XW6" FT STRAND 442..444 FT /evidence="ECO:0007829|PDB:7XW5" FT HELIX 448..477 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 481..483 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 485..490 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 492..524 FT /evidence="ECO:0007829|PDB:7XW6" FT TURN 525..527 FT /evidence="ECO:0007829|PDB:7T9M" FT HELIX 529..531 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 535..558 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 577..608 FT /evidence="ECO:0007829|PDB:7XW6" FT STRAND 611..613 FT /evidence="ECO:0007829|PDB:7T9M" FT HELIX 618..648 FT /evidence="ECO:0007829|PDB:7XW6" FT TURN 656..658 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 659..665 FT /evidence="ECO:0007829|PDB:7XW6" FT TURN 666..668 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 669..678 FT /evidence="ECO:0007829|PDB:7XW6" FT TURN 679..681 FT /evidence="ECO:0007829|PDB:7XW6" FT HELIX 683..693 FT /evidence="ECO:0007829|PDB:7XW6" FT TURN 694..696 FT /evidence="ECO:0007829|PDB:7XW6" FT CONFLICT P16473-2:239 FT /note="L -> F (in Ref. 6; AAB24246)" FT /evidence="ECO:0000305" FT CONFLICT P16473-2:248 FT /note="R -> S (in Ref. 5; AAB23390 and 9; FT AAH09237/AAI20974)" FT /evidence="ECO:0000305" FT CONFLICT P16473-2:251 FT /note="M -> T (in Ref. 5; AAB23390)" FT /evidence="ECO:0000305" FT CONFLICT P16473-3:269 FT /note="R -> S (in Ref. 9; AAI27629)" FT /evidence="ECO:0000305" SQ SEQUENCE 764 AA; 86830 MW; D2EE9CEBFD64A65F CRC64; MRPADLLQLV LLLDLPRDLG GMGCSSPPCE CHQEEDFRVT CKDIQRIPSL PPSTQTLKLI ETHLRTIPSH AFSNLPNISR IYVSIDVTLQ QLESHSFYNL SKVTHIEIRN TRNLTYIDPD ALKELPLLKF LGIFNTGLKM FPDLTKVYST DIFFILEITD NPYMTSIPVN AFQGLCNETL TLKLYNNGFT SVQGYAFNGT KLDAVYLNKN KYLTVIDKDA FGGVYSGPSL LDVSQTSVTA LPSKGLEHLK ELIARNTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM CNESSMQSLR QRKSVNALNS PLHQEYEENL GDSIVGYKEK SKFQDTHNNA HYYVFFEEQE DEIIGFGQEL KNPQEETLQA FDSHYDYTIC GDSEDMVCTP KSDEFNPCED IMGYKFLRIV VWFVSLLALL GNVFVLLILL TSHYKLNVPR FLMCNLAFAD FCMGMYLLLI ASVDLYTHSE YYNHAIDWQT GPGCNTAGFF TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHACA IMVGGWVCCF LLALLPLVGI SSYAKVSICL PMDTETPLAL AYIVFVLTLN IVAFVIVCCC YVKIYITVRN PQYNPGDKDT KIAKRMAVLI FTDFICMAPI SFYALSAILN KPLITVSNSK ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK RQAQAYRGQR VPPKNSTDIQ VQKVTHDMRQ GLHNMEDVYE LIENSHLTPK KQGQISEEYM QTVL //